DAIDZIN INHIBITS MITOCHONDRIAL ALDEHYDE DEHYDROGENASE AND SUPPRESSES ETHANOL INTAKE OF SYRIAN GOLDEN-HAMSTERS

Daidzin is the major active principle in extracts of radix puerariae, a traditional Chinese medication that suppresses the ethanol intake of Syrian golden hamsters. It is the first isoflavone recognized to have this effect, Daidzin is also a potent and selective inhibitor of huma n mitochondrial aldehyde dehydrogenase (ALDH-2). To establish a link b etween these two activities, we have tested a series of synthetic stru ctural analogs of daidzin, The results demonstrate a direct correlatio n between ALDH-2 inhibition and ethanol intake suppression and raise t he possibility that daidzin may, in fact, suppress ethanol intake of g olden hamsters by inhibiting ALDH-2. Hamster liver contains not only m itochondrial ALDH-2 but also high concentrations of a cytosolic form, ALDH-I, which is a very efficient catalyst of acetaldehyde oxidation, Further, the cytosolic isozyme is completely resistant to daidzin inhi bition, This unusual property of the hamster ALDH-1 isozyme accounts f or the fact we previously observed that daidzin can suppress ethanol i ntake of this species without blocking acetaldehyde metabolism, Thus, the mechanism by which daidzin suppresses ethanol intake in golden ham sters clearly differs from that proposed for the classic ALDH inhibito r disulfiram. We postulate that a physiological pathway catalyzed by A LDH-2, so far undefined, controls ethanol intake of golden hamsters an d mediates the antidipsotropic effect of daidzin.